Tuesday 27 March 2018

Why Outcrossing is Not a Panacea

This post is Part 4 in a series of articles on genetic diversity, breed conservation, and genetic tests. For links to all the articles, click here.


This is Saffi. When Saffi was a puppy, she liked to sit on the windowsill. She still tries to sometimes, although she doesn't really fit any more.

Saffi is the daughter of my Indi and her sire is a red poodle dog whom I chose to use on her because, along with other reasons, his pedigree was very different to Indi's. Saffi has a 15-generation COI of just under 5%. To put that in human timescales, a 15-generation pedigree would be all a person's ancestors going back to the 1600s. COI is a probability-based estimate of something called heterozygosity, the similarity between the two 'halves' of the genome inherited from each parent.

Before I get into this, let me just say that COI/heterosis isn't the only factor that should be taken into account when making breeding decisions. It should not just be a race to the bottom. However, the reason Saffi's DNA analysis looks the way I'm about to show here did not happen by accident.

The following graph is an analysis of Saffi's DNA by Genoscoper. Genoscoper's analysis looks at genetic markers in the DNA and estimates heterozygosity from this. Saffi is more heterozygous than the majority of poodles. In fact, she is within the same range as most mixed-breed dogs that Genoscoper has analysed.


Genoscoper is one of two tests I'm aware of that are currently available that analyse DNA to estimate genetic diversity. The other one is VGL. What's cool about VGL is that it gives you a PDF with 35 pairs of DNA markers on and you can put these numbers into third-party software such as SPD and number-crunch them to give estimates of heterosis and other measures of genetic diversity in potential breedings. On SPD, these are expressed as IR (heterosis, more negative numbers are more heterozygous and more positive ones are more homozygous) and OI (higher numbers are more unusual compared to the breed as a whole. VGL has also published some example certificates for different breeds on its website. I thought it might be interesting to compare these dogs to poodles, so I entered some of the data into the SPD.

I recently announced on my blog that I'm hoping to mate Hobsey when she next comes in heat. Obviously I am going to mate Hobsey to a poodle. But let's suppose I wanted to mate Hobsey to something that would be really different from her, so I mated her to my sister's Dobermann. Let's see how that would work:


Nota bene: This is an example Dobermann from VGL, and not my sister's Dobermann, who is in actuality castrated and we're not even sure if he is a real Dobermann.

The IR has a positive value of 0.02. That doesn't look awful, but the zero point is set for poodles, and negative numbers indicate more heterozygosity. There are many poodles that Hobsey could be mated with that would give a number in this range or better. The OI is 0.32, which is again OK, but not the fantastic result one might expect from such a radical step, and there are again many poodles alive and well with higher numbers than this.

How is it that two dogs of different breeds can produce pups of the same ballpark heterozygosity as two of the same breed? Well, they are both DOGS. The oldest bottleneck event was domestication. So some genetic markers are going to be ubiquitous throughout all domestic dogs.

Let's return to the subject of Saffi again. Her VGL analysis gives her a OI of 0.42 and an IR of -0.24. Which is better on both counts than the result here. I can have a more diverse dog by just breeding two poodles together. In fact, one of the conclusions of the original VGL study on poodles was that there is a reasonable amount of genetic diversity in poodles, but that it's unbalanced, and that breeders making breeding decisions to rebalance it would benefit the breed. I'm the first to admit that Saffi is not perfect, but I'm sure she's a damn sight better example of the breed in every single respect than this hypothetical puppy from Hobsey and a Dobermann.

Now, let's try something else. Let's pretend the gamekeeper down the road has a Flatcoat Retriever who is gorgeous and has a lovely temperament (and the dog isn't bad either). As there is a fad for novelty mix-breed dogs, and the price you can claim to them seems to be proportional to how stupid a portmanteau marketing name you can invent, let's say Saffi's mother Indi mated with this Flatcoat and I put an advert on a second-hand website for 'Poo Coat Retrievers'. And I kept a boy puppy... let's call him Matt. His coat is not very pleasant... kind of smelly and greasy, and sheds and gets tangled up, but he has that poodle trait of wanting to be on your lap all the time, and he's kind of a hyperactive lunatic, but he's never bitten me or done anything really horrible so I claim he has a wonderful temperament.

Here is an example of how Matt might look by VGL analysis. I just took the top alleles from a Flatcoat example and the bottom ones from Indi. This outcross works better than the last one, and Matt's done pretty well diversity-wise. He has a good IR in the negative range, and a OI of greater than 0.6, which is something hard to find in the poodle gene pool.


So, I try to recover the type by putting Matt over Hobsey. Let's see how that might come out:


Even though Matt worked quite well as an outcross from a genetic diversity standpoint, it's clear his benefits are much diminished another generation in. The IR is still negative, but only just, and the OI is better than average but not by a great deal, being in a range equal to many full-blood poodles. It's certainly not the quantum leap that might be hoped for in doing such a breeding. Saffi, a real poodle from two poodle parents, still has a result that is better on both counts than this, and Matt and Hobsey's puppy that I kept might have a more poodle-like temperament than her sire, but her coat is still horrible and she doesn't look very poodly.

As the above explains, putting dogs of two different breeds together is not a guarantee of great heterozygosity. More unrelated dogs are more likely to produce more heterozygous offspring, but it's not a given. What outcrossing breeds generally does do is introduce genes that are 'different' but as the Indi and Matt example shows, that difference is subject to diminishing returns the further in generations you progress from the original outbreeding.

Unfortunately there are currently no examples VGL has for poodle-related breeds from the same 'curly water dog' landrace, which would have been interesting to see. Serious outcross programmes (i.e. not the silly examples above) generally use related breeds to get the benefit of genetic difference but minimise the risk of outbreeding depression, however, if these are not managed properly there can also be problems. Unless several breeders are working to the same master plan, there is a risk that outcrosses will be over- or under-bred and harm the gene pool. If I breed English Bog Dogs and I mate my English Bog Dog bitch to a French Bog Dog from the same landrace stock, and other English Bog Dog breeders shun me because of this and my bloodline comes to be seen as something contaminated and unusable, then when I get too decrepit to breed any more Bog Dogs and shuffle off my mortal coil, my bloodline dies with me, and whatever genetic diversity that was in my original line and in the outcross is lost. On the other hand, if the offspring of my French/English Bog Dog breeding is seen as successful by other English Bog Dog breeders, other people might use my dogs and French Bog Dogs as well, and may well even use the same sire because his owner is accommodating of him being used on foreign breeds, and the French outcross dogs become popular sires and overused bloodlines, with all the problems inherent to that. What has to happen in this case is that breeders agree one person will use a German Bog Dog, another a French, another an Irish, and so on, and that they will plan subsequent matings carefully to make sure all the new genetics are incorporated evenly into the breed.

If outcrossing is done carelessly and purely for the sake of heterosis, like the silly examples, without any consideration given to the function and form of the breed we are trying to preserve, outbreeding depression could occur. Outbreeding depression is when the offspring of two very different parents exhibit poor fitness and unwanted traits because of poor compatibility between different genes and the genetic environment. For example, if I were to breed my English Bog Dog to a Himalayan Hairless Handbag Dog using artificial insemination because it's the most 'different' dog I can think of, I doubt the results would be very good for the Bog Dog's original purpose. If the Bog Dog is dolichocephalic, and the Handbag Dog is brachycephalic, there might well be dentition problems and very abnormal bites. The Bog Dog and related breeds are fictitious creations for the purpose of this blog post, as are the Himalayan Hairless Handbag Dogs. In the example of Matt, the poor coat and hyperactive temperament are possibly mild manifestations of this sort of issue.

I'm not lying about outbreeding depression. It is a real phenomenon that's been documented in nature. On another subject close to my heart, alpacas produced some of the finest fibre in the world until war and destruction in their native land caused them to interbreed with llamas. Now there are thought to be hardly any alpacas left alive that do not contain llama DNA, and the fleece has deteriorated accordingly, and is only now after much selective breeding starting to approach what it once was. There's no reason to think that alpacas prior to this had a compromised gene pool, and it has had no benefit to the alpacas. The only antidote for outbreeding depression is brutally aggressive selection over many generations to try to get rid of the deleterious genes that were introduced. Because aggressive selection always results in loss of diversity, there is a real risk that as breeders try to select back for the correct type and inadvertently breed away from an injudicious outcross, diversity will be lost, both the diversity introduced with the outcross as well as in the original breed parent.

Outcrossing to other breeds can potentially deflect attention from the vital work of preserving the diversity that already is in the breed's gene pool. Notice how Saffi is more diverse than Matt's offspring? If I only had room to keep one puppy from Indi, and I did this mating and used Matt instead and was eager to retire him and move forward with his offspring because of his lack of type, Saffi would never have been born and her contribution to the gene pool would not be there. Outcrossing is often seen as an easier path to newcomers to a breed rather than familiarising oneself with bloodlines and doing a lot of pedigree research, and trying to track down rare lines. Some of these rare lines have ended up in the hands of not very salubrious breeders, and accessing others might involve trips to foreign countries. Personally I have a rare British breed of chicken, and doing an outcross to a breed that looks phenotypically similar that I can buy eggs from off Ebay is looking a lot easier than trying to track down elderly, technologically illiterate, and hard to find breeders who have the genetic diversity that already exists in the breed and working out how related these remnants might be to each other. Slogging through a few generations of chickens to recover the type looks easier than travelling all over the country to obtain birds that might keel over before they manage to breed because of issues probably caused by inbreeding depression in the hope that they might be different enough to each other that the offspring will thrive and breed normally. But it's better for the breed in the long run to try to save what already exists first rather than letting it die out in pursuit of bringing in new material. Outcrossing with other breeds needs to be a last resort, and every other possibility for keeping the gene pool viable and hanging on to the unique genetics of the breed has to be pursued as a first priority. Once the original diversity of a breed is lost, it is lost forever.

Outcrossing can be a lifeline for a breed that is in dire genetic straits, and has been used successfully in many breeds, in Dalmatians, Setters, and Barbets, and in countless poultry breeds. But it's not a panacea for everything, and in rare breeds and endangered species that have sustainable genetic diversity, it can introduce more problems than it resolves, waste resources that would be better used for more important genetic conservation within the population, and even contribute to loss of diversity. It shouldn't be used without a great deal of caution and research to make sure that firstly it is necessary on a case-by-case basis, and lastly that when it is needed, the diversity it introduces isn't inadvertently squandered in subsequent generations.

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